Synthesis, Characterization, and Binding to the Translocator Protein (18 kDa, TSPO) of a New Rhenium Complex as a Model of Radiopharmaceutical Agents

Abstract

Abstract A new tridentate 2‐phenyl‐imidazopyridin‐dipropylacetamide ligand (CB239‐H) with high (nanomolar) affinity for the TSPO protein was synthesized and its coordination compound with rhenium tricarbonyl, fac ‐[Re(CO) 3 (CB239‐ N , N , O )] was investigated. The procedure established for the synthesis of the 187/185 Re complex can be also used for the synthesis of 99m Tc and 188/186 Re analogues, which find application in SPECT diagnosis and in therapy. Because of the tridentate coordination of CB239‐H and the kinetic inertness of the carbonyl ligands, the new complex was expected to exhibit low reactivity towards plasma proteins and hence greater resistance to deactivation. Being TSPO overexpressed in numerous types of cancers and in activated microglial cells occurring in inflammatory neurodegenerative diseases, TSPO ligands can be exploited as carriers for receptor‐mediated drug targeting and hence can be used in diagnosis as well as in therapy. Very suprisingly, fac ‐[Re(CO) 3 (CB239‐ N , N , O )] resulted to be not very stable in diluted human serum but maintained a good affinity towards TSPO.